Main research line is the study of the structure-function relationship in enzymes from the viewpoint of understanding the determinants that underlay (thermal)stability and the molecular processes which control the substrate recognition, enzyme inhibition and enzyme catalysis. The tasks are approached mainly by studying enzymes from (hyper)thermophilic sources, mainly from Archaea and are also performed by comparison with mesophilic, homologous counterparts, which allow tracing back evolution of enzyme activity by looking at sequence/structure hallmarks and promiscuous activities. Furthermore, the potential uses of these enzymes in the industry, for the environment and for human health are investigated. Recently focus has been made on some human proteins (PON2, Pyruvate dehydrogenase complex) and their role in many diseases (cancer, type 2 diabetes, atherosclerosis and related complicancies).
Our group’s research focuses on the following topics:
- Study of structure/function relationship, protein-protein interactions and comparative analysis of carboxylesterases belonging to the Hormone Sensitive Lipase (HSL) family from mesophilic, thermophilic and hyperthermophilic sources.
- Study of structure/function relationship and comparative analysis of phosphotriesterases belonging to the amidohydrolase superfamily from mesophilic, thermophilic and hyperthermophilic sources.
- Study of structure/function relationship of PARPSso and comparative analysis from mesophilic, thermophilic and hyperthermophilic sources.
- Application of thermostable carboxylesterases as biosensor and/or traps for organophos- phorous compounds, such as pesticides and nerve agents
- Application of phosphotriesterases from Archaea and soil bacteria as potential agents in decontamination/bioremediation of pesticides
- Tailoring of enzymes to the specific applications listed above through in vitro molecular evolution and structure-driven protein engineering
- Study of the structure/function relationship of human PON2. The protein has been made recombinant in E.coli and insect cells and studied in vitro and in vivo (cells, animal models). Post-translational modifications are investigated by nanoLC-MsMs spectroscopy.
- Modeling, docking analyses and structure resolution (in collaboration) of proteins of interest.
In addition to classical biochemical techniques we also rely on different competencies such as, microbiology, molecular biology, molecular modeling, protein chemistry, protein engineering, directed evolution, enzyme kinetics and inhibition, mass spectrometry and high throughput screening with a robotic workstation. These approaches are complemented with external collaborations in structural biology, protein chemistry, organic chemistry in Italy and abroad as well as strict cooperation with some industries.
Cetrangolo GP, Gori C, Rusko J, Sara Terreri , Giuseppe Manco, Amelia Cimmino, Ferdinando Febbraio.
Determination of Picomolar Concentrations of Paraoxon in Human Urine by Fluorescence-Based Enzymatic Assay. Sensors (Basel). 2019;19(22):4852. Published 2019 Nov 7. doi:10.3390/s19224852
Elena Porzio, Francesca Bettazzi , Luigi Mandrich, Immacolata Del Giudice, Odile F Restaino , Serena Laschi , Ferdinando Febbraio , Valentina De Luca, Maria G Borzacchiello , Teresa M Carusone, Franz Worek, Antonio Pisanti, Piero Porcaro , Chiara Schiraldi, Mario De Rosa, Ilaria Palchetti , Giuseppe Manco
Innovative Biocatalysts as Tools to Detect and Inactivate Nerve Agents. Sci Rep. 2018;8(1):13773. Published 2018 Sep 13. doi:10.1038/s41598-018-31751-5
Ferriero R, Nusco E, De Cegli R, Carissimo A, Manco G, Brunetti-Pierri N. Pyruvate dehydrogenase complex and lactate dehydrogenase are targets for therapy of acute liver failure. J Hepatol. 2018;69(2):325–335. doi:10.1016/j.jhep.2018.03.016
Ferriero R, Manco G, Lamantea E, Edoardo Nusco, Maria I Ferrante, Paolo Sordino, Peter W Stacpoole, Brendan Lee, Massimo Zeviani, Nicola Brunetti-Pierri.
Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis. Sci Transl Med. 2013;5(175):175ra31. doi:10.1126/scitranslmed.3004986
Elias M, Dupuy J, Merone L, Mandrich L, Porzio E, Moniot S, Rochu d, Lecomte C, Rossi M, Masson P, Manco G, Chabriere E (2008)
“Structural basis for natural lactonase and promiscuous phosphotriesterase activities” Journal of Molecular Biology 379:1017-1028.
Programs & Resources
- PON 01_01585 PRODOTTI INNOVATIVI PER IL MONITORAGGIO E LA DECONTAMINAZIONE / DETOSSIFICAZIONE DI AGENTI NERVINI ED ESPLOSIVI NELL’AMBIENTE E/O PER LA GESTIONE DELLE EMERGENZE
- POR CAMPANIA FESR Nuove strategie per la diagnostica medica e molecolare e per la tracciabilità ed il monitoraggio dei prodotti alimentari ” 2014-2020.
- “Proof of Concept” MIUR– “Innovative anti-biofilm systems for wound infections” 2019-2021.
- EU 2020 “DNA helicases in genome maintenance: from molecular and cellular mechanisms to specific inhibitors as potential drugs”.
Il Miur finanzia ‘Siabio’, il nuovo progetto di ricerca ‘proof of concept’ di Cnr-Ibbc
Un progetto del Sud come supporto alle emergenze che vedono coinvolti agenti neurotossici
L’Italia dei giovani leader del futuro: dottoranda Cnr-Ibp menzionata da Forbes
Due borse Fulbright BEST all’IBP CNR di Napoli
15 idee per il futuro. Ecco i progetti finalisti del premio Start-Cup 2011 organizzato da Cnr e Il Sole